Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma

Keith L Ligon; Emmanuelle Huillard; Shwetal Mehta; Santosh Kesari; Hongye Liu; John A Alberta; Robert M Bachoo; Michael Kane; David N Louis; Ronald A Depinho; David J Anderson; Charles D Stiles; David H Rowitch

doi:10.1016/j.neuron.2007.01.009

Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma

Neuron. 2007 Feb 15;53(4):503-17. doi: 10.1016/j.neuron.2007.01.009.

Authors

Keith L Ligon¹, Emmanuelle Huillard, Shwetal Mehta, Santosh Kesari, Hongye Liu, John A Alberta, Robert M Bachoo, Michael Kane, David N Louis, Ronald A Depinho, David J Anderson, Charles D Stiles, David H Rowitch

Affiliation

¹ Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

Abstract

Recent studies have identified stem cells in brain cancer. However, their relationship to normal CNS progenitors, including dependence on common lineage-restricted pathways, is unclear. We observe expression of the CNS-restricted transcription factor, OLIG2, in human glioma stem and progenitor cells reminiscent of type C transit-amplifying cells in germinal zones of the adult brain. Olig2 function is required for proliferation of neural progenitors and for glioma formation in a genetically relevant murine model. Moreover, we show p21(WAF1/CIP1), a tumor suppressor and inhibitor of stem cell proliferation, is directly repressed by OLIG2 in neural progenitors and gliomas. Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Basic Helix-Loop-Helix Transcription Factors / deficiency
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Brain Neoplasms / pathology*
Bromodeoxyuridine / metabolism
Cell Differentiation / physiology
Cell Proliferation
Cells, Cultured
Chromatin Immunoprecipitation / methods
Cyclin-Dependent Kinase Inhibitor p16 / deficiency
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Embryo, Mammalian
Flow Cytometry
Glioma / pathology*
Green Fluorescent Proteins / biosynthesis
Luciferases / metabolism
Mice
Mice, Inbred C57BL
Mice, SCID
Mice, Transgenic
Nerve Tissue Proteins / deficiency
Nerve Tissue Proteins / metabolism*
Neurons / physiology*
Oligodendrocyte Transcription Factor 2
Stem Cells / physiology*

Substances

Basic Helix-Loop-Helix Transcription Factors
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p21
Nerve Tissue Proteins
Olig2 protein, mouse
Oligodendrocyte Transcription Factor 2
Green Fluorescent Proteins
Luciferases
Bromodeoxyuridine

Abstract

Publication types

MeSH terms

Substances

Grants and funding